Pharmacotherapy for unresectable metastatic colorectal cancer

Unresectable metastatic colorectal cancer (mCRC) has a poor prognosis. Emerging treatment paradigms have improved outcomes in selected unresectable mCRC cases. Recent therapeutic advancements are due in part to a shift in trial designs. By examining CRC as a heterogeneous group of various tumor subtypes, researchers have identified molecular distinctions that have led to promising targets.

Nineteen antineoplastic agents are included in the National Comprehensive Cancer Network guidelines for the palliative management of mCRC. However, not all patients will be candidates for each agent. New therapies for rare mCRC subtypes have emerged. Herein, the authors review these rare mCRC subtypes: microsatellite instability-high/deficient mismatch repair, BRAFV600E-mutant, and human epidermal growth factor receptor 2-positive tumors. Additionally, they provide an overview of unresectable mCRC management and future directions.

Treatment in the majority of mCRC patients (RAS wild-type or RAS-mutant, microsatellite instability-stable or -low/mismatch repair-proficient, BRAFV600E wild-type, or HER2-negative) needs further advancement and remains an unmet need. The authors believe that the key to identifying more breakthroughs in these mCRC patients is to continue to differentiate their tumors molecularly and clinically.